1. Field of the Invention
The present invention relates to the use of an immunogenic composition comprising a porcine circovirus type 2 (PCV2) antigen for the prevention and treatment of porcine respiratory disease complex (PRDC) in animals, preferably in pigs.
2. Description of the Prior Art
Porcine circovirus type 2 (PCV2) is a small (17-22 nm in diameter), icosahedral, non-enveloped DNA virus, which contains a single-stranded circular genome. PCV2 shares approximately 80% sequence identity with porcine circovirus type 1 (PCV1). However, in contrast with PCV1, which is generally non-virulent, infection of swine with PCV2 has recently associated with a number of disease syndromes which have been collectively named Porcine Circovirus Diseases (PCVD) (also known as Porcine Circovirus associated Diseases (PCVAD)) (Allan et al. 2006, IPVS Congress). Postweaning Multisystemic Wasting Syndrome (PMWS) is generally regarded to be the major clinical manifestation of PCVD (Harding et al., 1997, Swine Health Prod; 5: 201-203; Kennedy et al., 2000, J Comp Pathol; 122: 9-24). PMWS affects pigs between 5-18 weeks of age. PMWS is clinically characterized by wasting, paleness of the skin, unthriftiness, respiratory distress, diarrhea, icterus, and jaundice. In some affected swine, a combination of all symptoms will be apparent while other affected swine will only have one or two of these symptoms (Muirhead, 2002, Vet, Rec.; 150: 456). During necropsy, microscopic and macroscopic lesions also appear on multiple tissues and organs, with lymphoid organs being the most common site for lesions (Allan and Ellis, 2000; J Vet. Diagn. Invest., 12: 3-14). A strong correlation has been observed between the amount of PCV2 nucleic acid or antigen and the severity of microscopic lymphoid lesions. Mortality rates for swine infected with PCV2 can approach 80%.
The extent of the involvement of PCV2 in swine diseases other than PMWS is currently poorly understood (Chae, Veterinary J., 2003; 169: 326-336). There are several potentially related conditions reported in the literature including porcine respiratory disease complex (PRDC), porcine dermatopathy and nephropathy syndrome (PDNS), reproductive failure, granulomatous enteritis and potentially, congenital tremors (CT-AII) and perinatal myocarditis (Chae, Veterinary J., 2005; 169: 326-336). Among these, PRDC is considered to have the greatest economical impact in Europe due to its general high prevalence, high morbidity rate (30-70% on affected farms) and mortality rate (4-6% on affected farms) (Kim et al., Veterinary J., 2003; 166: 251-256). Pneumonia in pigs suffering from PRDC is due to a combination of both viral and bacterial agents such as PRRSV, Swine influenza virus (SIV), Mycoplasma hyopnumoniae, Actinobacillus pleuropneumoniae and Pasteurella multocida. Although the aetiology involves multiple pathogens and varies from farm to farm, PRRSV and Mycoplasma hyopneumoniae are the two most common pathogens isolated from PCV2 positive pigs exhibiting PRDC (Kim et al., Veterinary J., 2003; 166: 251-256). Whether PCV2 plays any role in the cause of PRDC or in the manifestation, severity, or prolongation of clinical signs of PRDC is yet not known.
Compared with other viral pathogens PCV2 was consistently diagnosed in lung lesions of pigs suffering from PRDC. Prospective studies have documented that pneumonia and often systemic illness, resulting from co-infection with PCV2 and PRRSV is more severe than that associated with infection by either agent alone. It can therefore be assumed that there is an apparent synergy between PCV2 and other pathogens that has been observed in respiratory disease cases in the field (Ellis et al., Veterinary Microbiol, 2004: 98: 159-163). However, it is yet not known whether PCV2, if present in pigs suffering from PRDC, has any influence on the clinical signs of PRDC in pigs. Due to the ubiquity of PCV2 with up to 100% seropositive animals at the end of fattening, it may similarly be possible that PCV2 has no influence at ad on the disease expression of PRDC but is just an unrelated co-infecting agent.
Whereas PMWS mostly affects young pigs, typically between 5 and 12 weeks of age, PRDC is predominantly seen in growing to finishing pigs, typically around 16 to 22 weeks of age. The morbidity ranges from 30-70% with an average mortality of 4-6% (Kim et al., Veterinary J., 2003; 166: 251-256). Clinically signs of PRDC are prolonged and unusually severe cough and dyspnea that is refractory to antibiotic therapy, slow growth, decreased feed efficiency, lethargy, anorexia, and a marked increase in mortality in the middle to late phase of fattening.
A hallmark of microscopic lesions PRDC is bronchointerstitial pneumonia with peribronchial and peribronchiolar fibrosis. Alveolar septa are markedly thickened by infiltrates of macrophages (Chae. Veterinary J., 2005; 169: 326-336).
Approaches to treat PCV2 infections based on a DNA vaccine are described in U.S. Pat. No. 6,703,023. In WO 03/049703, production of a live chimeric vaccine is described, comprising a PCV-1 backbone in which an immunogenic gene of a pathogenic PCV2 strain replaces a gene of the PCV-1 backbone. WO99/18214 has provided several PCV2 strains and procedures for the preparation of a killed PCV2 vaccine. However, no efficacy data has been reported. An effective ORF-2 based subunit vaccine has been reported in WO06/072065, the teachings and content of which are incorporated by reference herein. Any of such vaccines are intended to be used for the vaccination/treatment of swine or pigs older than 3 weeks of age. None of these vaccines have been described for the prophylaxis or treatment of pigs suffering from PRDC, in particular in PCV2 positive pigs, suffering from PRDC.
Moreover, such vaccines have not been described to confer protective immunity against PCV2 infection or reducing, lessening the severity of or curing any clinical symptoms associated therewith in pigs already having anti-PCV2 antibodies, preferably having maternal anti-PCV2 antibodies.